ES2958918T3 - Dietary supplement to treat dysbiosis - Google Patents

Abstract

Disclosed are a dietary supplement and methods of manufacture and administration for the treatment and/or prevention of digestive disorders and disorders related to the immune system. The dietary supplement may be administered orally and may be composed in solid form (including sticks, wafers or tablets), in paste form, in granular form, in powder form or in liquid form. The ingredients of the dietary supplement of the present invention when combined provide synergistic efficacy that greatly exceeds the sum of the efficacies of the individual ingredients, making the dietary supplement highly effective in the treatment and/or prevention of digestive disorders and disorders related to the immune system. . The dietary supplement of the present invention is composed to increase the impermeability of the intestinal lining as well as to balance the bacterial components of the microbiota, thereby minimizing systemic inflammation, the cause of most chronic diseases. (Automatic translation with Google Translate, without legal value)

Description

DESCRIPTION

Dietary supplement

field of invention

This invention relates generally to dietary supplements for humans and animals, and more particularly to a novel dietary supplement for use in the treatment and/or prevention of dysbiosis and diseases associated with dysbiosis.

Background of the invention

Researchers are increasingly finding that human gut microbes (collectively known as microbiota), through their protective effect on the intestinal lining and their moderating influence on the immune system, are important factors in maintaining good health. Document US 2005/0058671 refers to a dietary supplement for the treatment and prevention of the digestive system and disorders related to the digestive system, said digestive supplement comprising: polar lipid supplement containing significant amounts of polar lipids and antioxidants; soluble beta-glucan fiber that provides at least one beneficial health effect; and at least one amino acid that provides at least one beneficial effect on the digestive system.

Humans acquire a microbiota at birth as they go down the birth canal. If they are born via C-section, they instead collect a microbiota from the nurses and the hospital. Breastfed babies are also seeded with bacteria that live in breast milk, along with prebiotics (oligosaccharides that feed the microbiota). Babies born by cesarean section who are formula-fed therefore lose two important mechanisms for starting a healthy microbiota.

Diseases such as food poisoning can also alter the intestinal microbiota. This alteration is called dysbiosis, and it can lead to a thinning of the mucosal layer that lines the entire intestine, as well as damage to the enterocytes that make up the intestinal lining. When the intestinal lining breaks down, bacteria can escape from the intestine and lead to systemic infection. The body responds by launching an immune attack on circulating bacteria that can reach every organ in the body. The immune system often produces collateral damage, destroying human cells along with bacteria. If the infection persists, the inflammation can become chronic.

Long-term systemic inflammation has been linked to virtually every chronic disease, from heart disease to neurological problems. To compensate for this problem, the intestinal lining must heal to stop the flow of pathogens into the bloodstream. Two therapies are used to treat dysbiosis: probiotics (live beneficial bacteria) and prebiotics in the form of various oligosaccharides that nourish the beneficial bacteria.

There are six outcomes of gut dysbiosis considered herein: gut inflammation, systemic inflammation, neurological inflammation, antibiotic-induced inflammation, autoimmunity, and chemotherapy.

intestinal inflammation

Intestinal inflammation is the first and most direct effect of dysbiosis. It takes the form of gastric ulcers, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD, which consists of ulcerative colitis and Crohn's disease), colon cancer and rectal cancer. Each of these syndromes is associated with leaky gut. Gastric ulcers can currently be treated with antacids and proton pump inhibitors. However, very recent research indicates that both treatments, by raising gastric pH, can create a harmful environment for the colon. There are currently very few options for IBS or IBD, although fecal microbial transplants are beginning to be used with variable effect. Bowel cancers are treated with surgery, chemotherapy and radiotherapy, which have their own problems (see below).

Systemic inflammation

Systemic inflammation leads to heart disease, type 2 diabetes, various cancers, allergies and other organic diseases. Heart disease can be treated with surgery, implanted pacemakers/cardioverters, and a variety of drugs, including statins, blood thinners, ACE inhibitors, and beta blockers. Type 2 diabetes can be controlled with insulin, diet and exercise. Cancers are treated with surgery, chemotherapy treatments, and radiation. Allergies can be treated with antihistamines.

Neurological inflammation

Neurological inflammation takes longer to evolve from the gut, through various gut-brain pathways. Parkinson's begins with Lewy bodies that infect intestinal cells and cause constipation before they make their way to the brain over a period of ten years. Alzheimer's may also represent a movement of misfolded amyloid proteins originating in the gut that similarly move to the brain over time. Depression and anxiety are also linked to dysbiotic gut. There are no cures for Parkinson's or Alzheimer's. Certain symptoms of Parkinson's can be treated with L-dopa, but that can also create dyskinesia. Depression and anxiety can be treated with serotonin reuptake inhibitors (SRIs) and other drugs that attempt to raise brain levels of dopamine, serotonin, gamma-amino butyric acid (GABA), and norepinephrine. These drugs don't work for many people, and when they do, they tend to cause weight gain.

Antibiotic-induced inflammation

Antibiotics have saved millions of lives that would otherwise have been lost due to bacterial infection. But today, antibiotics are overused, and oral administration (as opposed to parenteral administration), in many hospital settings, has been shown to actually increase inflammation. In particular, infections byC. diff, as a consequence of the administration of antibiotics, cause half a million infections a year, and the mortality rate is close to 30,000 people a year. Oral antibiotics, by decimating normal gut microbial populations, have been shown to increase intestinal permeability, allowing live bacteria to enter the bloodstream and create systemic inflammation.

Autoimmunity

Autoimmunity is thought to be a problem caused by mimicry, where bacteria or their products have close similarities to existing body tissues. When the immune system attacks these foreign particles, it can also attack normal tissue that shares certain antigenic properties. These diseases include arthritis, lupus, type I diabetes and multiple sclerosis. There are no cures for these diseases. Type I diabetes can be treated with insulin, but drugs for autoimmune diseases are mainly experimental.

Chemotherapy and radiation treatments

Chemotherapy and radiation treatments work by attacking rapidly dividing cells, because cancer cells undergo unusually rapid turnover. However, these drugs and treatments are not perfectly targeted, and they also destroy cells that normally have short lifespans, including hair follicles and the lining of the intestine, which renews itself weekly. These cancer treatments, then, can lead to leaky gut and induce the whole host of diseases listed above. Specific illnesses directly attributable to cancer treatments include mucositis, stomatitis, cachexia, and diarrhea. In the context of cancer therapy, these diseases are resistant to treatment, and the overall prognosis depends on the length and intensity of cancer therapy. New cancer treatments involving immune checkpoint inhibitors depend on a well-balanced microbiota. Thus, appropriate prebiotic fibers can augment these novel immune cell therapies.

Leaky intestinal tissues leading to systemic inflammation

A large percentage of chronic diseases, including heart disease, diabetes, obesity, IBD, IBS, arthritis, Alzheimer's and Parkinson's, are strongly associated with intestinal dysbiosis, in particular, increased intestinal permeability (termed “leaky gut”). Bacteria that enter the bloodstream can be pumped to each and every organ in the body, thus spreading inflammation throughout the system. Inflammation is a supposed precursor to the diseases mentioned above. It follows, then, that a product that can heal a leaky gut can reduce systemic inflammation and decrease the incidence of chronic disease.

Prebiotics are known to increase the number of beneficial microbes that produce short chain fatty acids (SCFAs) which, in turn, can accelerate the repair and regeneration of damaged tissue in the intestine. However, boosting microbes in the presence of a highly permeable intestinal lining may risk systemic inflammation.

Because all of these diseases are associated with inflammation, there has been success treating them with prebiotics and probiotics. The preponderance of evidence points to the need to balance the microbiota to prevent, improve or cure these many chronic diseases of inflammation.

As such, there is a need in the art for a dietary supplement that synergistically addresses the above issues. The invention provides such a dietary supplement. These and other advantages of the invention, as well as additional inventive features, will be apparent from the description of the invention provided herein.

Brief summary of the invention

References to therapy treatment methods in this description should be construed as references to the compositions of the present invention for use in those methods.

The main objective of the present invention is to treat dysbiosis and its consequent effect on the intestinal lining and ultimately the corresponding immune response in humans and potentially also in other animals. In addition to treating these diseases, the present invention also aims to prevent dysbiosis and its consequent diseases.

A further objective of the present invention is to use only safe ingredients. The present invention is gluten-free, allergen-free, GMO-free, milk-free, egg-free, nut-free and preservative-free, with no artificial additives. Furthermore, it is intended that the present invention be conveniently consumed orally in the form of a paste, a solid (such as a bar, a pressed pill or a cookie), a liquid or a powder that can be consumed alone or mixed with other foods. or drinks. A further objective of the present invention is to make shipping and storage easy and convenient.

The present invention has been designed to be stable with a commercially acceptable shelf life. The present invention is relatively inexpensive compared to drugs that aim to heal the intestine, such as proton pump inhibitors. All of the above objectives have been designed to avoid any substantial relative disadvantage with respect to current treatments.

With this invention, there is provided a novel dietary supplement that is formulated to treat and/or prevent various disorders of the digestive tract and also various disorders related to the immune system. Through periodic administration of this dietary supplement to humans or other animals according to the methods taught by the present invention, various disorders of the digestive tract and various disorders related to the immune system are effectively treated and/or prevented in such humans. and other animals. As will be evident to those skilled in the art, the dietary supplement of the present invention is much more than the sum of its ingredients, with the combination of ingredients producing a synergistic result substantially more effective than the results that would be produced if each of the ingredients that acts by itself will be provided to humans or other animals.

The dietary supplement of the present invention can be manufactured in several different forms, which can either be taken directly as a dietary supplement or added to foods or beverages. The dietary supplement of the present invention can be manufactured as a solid, granulated solid, powder, paste or liquid. To manufacture it as a solid, a small amount of oat bran or oat flour (or substitutes thereof) is added to thicken it into a food stick or to allow it to be pressed into pill form. By adding a higher percentage of oat bran or oat flour while stirring the mixture, a granular form of the supplement can be manufactured. By adding even more flour, a powder form of the supplement can be made. By adding more oil (oat oil, sunflower oil, safflower oil, or another oil), the mixture can be brought to a paste that has the consistency of peanut butter. By adding even more oil, it can become a viscous liquid.

The dietary supplement of the present invention can also be manufactured as a liquid, powder or paste and stored in a gelatin capsule (such as gel capsules), which provides a constant dosage of the dietary supplement. It is desirable that the dietary supplement of the present invention be taken on a regular basis, which in the preferred embodiment is daily or several times a day (e.g., with meals) to maintain an optimal level of the ingredients in the digestive tract.

Upon disclosure of the dietary supplement of the present invention to those skilled in the art, they will immediately appreciate that the dietary supplement is much more than simply the sum of its ingredients.

Depending on the particular desired application of the dietary supplement of the present invention, additional constituents such as vitamins and minerals may also be added thereto.

Therefore, it can be seen that the present invention teaches a dietary supplement that effectively treats disorders of the digestive tract as well as disorders related to the immune system in humans and also in other animals. The dietary supplement of the present invention consists entirely of safe ingredients instead of drugs. The dietary supplement of the present invention can be administered orally, thereby making its dispensing a simple matter. The dietary supplement of the present invention can be combined in paste form, in solid form, a liquid form or in a powder or granular form that can be added to liquids for administration. The dietary supplement of the present invention may also be packaged in a manner that facilitates transportation, storage and consumption.

The dietary supplement of the present invention is stable and has a long shelf life, and does not require any special care from the user throughout its shelf life before use. The dietary supplement of the present invention is also economical relative to previously known treatments of digestive tract disorders and treatments of immune-related disorders, thereby enhancing its market appeal and providing it with the widest possible market. Finally, all of the above-mentioned advantages and objectives of the dietary supplement of the present invention and its method of administration are achieved without incurring any substantial relative disadvantages.

In view of the above, one aspect of the invention presents a dietary supplement for the treatment and prevention of dysbiosis and diseases associated with dysbiosis. The dietary supplement includes:

L-glutamine;

at least one of the following mucogenic amino acids: L-threonine, L-serine, L-proline, L-cysteine;

lecithin;

fructo-oligosaccharide;

beta-glucan;

RS-4 starch; and

arabinoxylan oligosaccharide.

In one embodiment according to this aspect, L-glutamine is produced by vegan bacterial fermentation of sugar beet, isolated, purified and micronized for better and faster absorption. The L-glutamine included comprises between approximately one percent and twenty percent of said dietary supplement by weight. In an embodiment according to this aspect, the at least one mucogenic amino acid is produced by vegan bacterial fermentation, isolated and purified. Each of the at least one mucogenic amino acid comprises between about zero percent and ten percent of said dietary supplement by weight.

In one embodiment according to this aspect, the lecithin is derived from soybean oil, oat oil, sunflower oil, safflower oil or corn oil. Lecithin comprises between about one percent and about fifteen percent of said dietary supplement by weight.

In one embodiment according to this aspect, the fructo-oligosaccharides are derived from yacon root, chicory root, Jerusalem artichoke or blue agave. Fructo-oligosaccharides comprise between about one percent and about forty percent of said dietary supplement by weight.

In one embodiment according to this aspect, the beta-glucan is derived from oats, barley, mushrooms, seaweed, algae or yeast cell walls. Beta-glucan comprises between about one percent and about forty percent of said dietary supplement by weight.

In one embodiment according to this aspect, the arabinoxylan oligosaccharide is derived from the bran tissues of wheat, oats, barley, rice, millet, psyllium, flax or rye. The arabinoxylan oligosaccharide comprises between about one percent and about forty percent of said dietary supplement by weight.

In one embodiment according to this aspect, the RS-4 starch is derived from oats, yacon root, chicory root, flax, acacia, corn or bacterial fermentation and then undergoes chemical cross-linking to decrease digestibility by human acids and enzymes. RS-4 starch comprises between about one percent and about forty percent of said dietary supplement by weight.

In an embodiment according to this aspect, the dietary supplement also includes a nutricin that binds to and eliminates pathogenic bacteria in the digestive tract, the nutricin including at least one of pure mannan or mannan oligosaccharide (MOS). Nutricin that binds to and kills pathogenic bacteria in the digestive tract comprises between about half percent and about forty percent of said dietary supplement by weight.

In an embodiment according to this aspect, the dietary supplement also includes a medication that is carried with the other ingredients of said dietary supplement, wherein at least one of the absorption or therapeutic value of said medication is maximized when taken together with said dietary supplement. .

In embodiments according to this aspect, the dietary supplement may be combined as solid food bars, as a paste, as a granulated solid, as a powder, as a liquid, and/or as liquid-filled soft gel capsules.

In one embodiment according to this aspect, disorders of the digestive system are selected from a group comprising ulcers, colitis, irritable bowel syndrome, diverticulosis, diverticulitis, Crohn's disease, mucositis, and stomatitis. In embodiments according to this aspect, wherein said disorders related to the digestive system are selected from a group consisting of cachexia, lactose intolerance and dietary insufficiencies in the elderly. In embodiments according to this aspect, immune system related disorders are selected from a group comprising arthritis, diabetes, depression, anxiety and heart disease. In embodiments according to this aspect, the related disorders are selected from a group comprising Alzheimer's, Parkinson's, multiple sclerosis and other neurodegenerative diseases.

In embodiments according to this aspect, the dietary supplement also includes at least one vitamin from the group consisting of vitamin B6, vitamin B12, biotin, vitamin C, vitamin D, vitamin E and niacin.

In embodiments according to this aspect, the dietary supplement also includes at least one mineral micronutritional additive selected from the group consisting of calcium, chromium, copper, manganese, magnesium, manganese, phosphorus, potassium, selenium, vanadium and zinc.

In embodiments according to this aspect, taking a daily dosage of between about ten grams and about sixty grams of said dietary supplement daily provides effective amounts of said lecithin, said beta glucan and said amino acids.

In another aspect, the invention provides a method of administering the dietary supplement as described above for use in the treatment and prevention of disorders related to the immune system and the digestive system. One embodiment of such a method includes preparing a dose of dietary supplement of appropriate size and administering said dietary supplement on a regular basis. The method may also include repeating said administration step at least once a day.

The disadvantages, limitations and high cost of the existing prior art discussed above are overcome by the present invention. Other aspects, objects and advantages of the invention will become more apparent from the following detailed description when taken together with the accompanying drawings.

Brief description of the drawings

The accompanying drawings incorporated and forming part of the specification illustrate various aspects of the present invention and, together with the description, serve to explain the principles of the invention. In the drawings:

Figure 1 is a schematic drawing of a human showing the anatomy of the human digestive tract; Figure 2 is a schematic diagram showing the prebiotics of the present invention against the portions of the digestive tract and flora they target; and

Figure 3 is a graph of the absorption rate of amino acids.

Detailed description of the invention

Prior to a discussion of the nutritional product of the present invention and the methods of preparation and administration thereof, it is useful to briefly discuss the anatomy of the human digestive system. With reference to the figure, the head and torso of a human being are illustrated together with a schematic illustration of the human digestive tract. The digestive tract of a human begins in mouth 1, and extends sequentially through esophagus 2 and into stomach 4. In the mouth, food is chewed and saliva mixes with the food to begin digestion of the food. carbohydrates. The food is swallowed, and passes through the esophagus to the stomach, where pepsin helps in the digestion of the protein.

From the stomach, food flows through the duodenum 5, which is the first portion of the small intestine 7, where chemicals secreted by the liver 3 and pancreas 6 allow the duodenum to break down fat. From the duodenum, food then moves to the small intestine 7, where the digestion process is completed and intestinal bacteria are found. The digested food then moves to colon 8, where water and sodium are eliminated and where most of the gut microbiota is found, and then to rectum 9. The remaining undigested solids then exit the body through the anus. 10.

The dietary supplement of the present invention includes several main components, each of which provides a beneficial health effect that is facilitated by the inclusion of a particular ingredient or mixture of ingredients in the dietary supplement. During the following discussion of the ingredients of the dietary supplement of the present invention, it will quickly become apparent to those skilled in the art that the benefits achieved by the dietary supplement of the present invention are substantially greater than the sum of the individual benefits of each of the ingredients. the ingredients of the dietary supplement. Briefly, these various components include:

L-glutamine;

one or more polar mucogenic amino acids that increase the number and productivity of goblet cells lining the intestine to improve protection against pathogens in the intestinal lumen, in particular, at least one of L-threonine, L-serine, L-proline , L-cysteine;

lecithin which is included to increase the bioavailability and absorption rate of the above polar amino acids to allow them to act before the following prebiotics act;

Fructo-oligosaccharide (FOS), a prebiotic that works primarily in the distal ileum and ascending colon to support beneficial microbes, especially Lactobacillus and Clostridium species, in this area of the GI tract;

beta-glucan, a prebiotic that works primarily in the ascending and transverse colon, to support beneficial microbes, especially Bifidobacterium and Faecalibacterium species, in this area of the GI tract;

RS-4, a resistant chemically modified corn starch, a prebiotic that works primarily in the transverse and descending colon, to support beneficial microbes, especially Lachnospiraceae and Roseburia species, in this area of the GI tract; and

Arabinoxylan oligosaccharide (AXOS), a prebiotic that works primarily in the descending colon and rectum, to support beneficial microbes, especially Veilonella and Prevotella species, in this area of the GI tract.

As will be understood from the disclosure herein, the invention effectively presents a two-part formulation. This first part of this formula includes L-glutamine, one or more mucogenic amino acids, and lecithin. These constituents act first by healing the intestine by enhancing tight junctions and improving the mucus layer in the intestine. An improved absorption rate of amino acids is provided by the inclusion of lecithin. The second part of this formula includes prebiotics, which improve the intestinal microbiota as discussed herein. There is a synergistic effect between these two parts. Without first healing the gut, tightening cell junctions and boosting the mucosa, there is a risk that prebiotics can escape from the gut and therefore not provide their beneficial effects.

Glutamine and one or more mucogenic amino acids work together to aid in the absorption of nutrients. In particular, people with leaky gut may not benefit from the inclusion of the prebiotics mentioned above. Additional induced bacteria can leak into the bloodstream through the intestinal lining. The addition of L-glutamine and a mucogenic amino acid helps to quickly heal the intestinal lining so that additional commensal bacteria will remain in the intestine. Furthermore, the applicant has discovered that the mucogenic amino acid increases the mucosa thereby improving the fidelity of the intestinal lining. This, in turn, reduces or eliminates the likelihood of additional commensal bacteria escaping from the intestine. The L-glutamine used herein can be produced, by way of non-limiting example, by vegan bacterial fermentation of sugar beets, isolated, purified and micronized.

L-glutamine is a preferred food for the enterocytes and colonocytes that line the intestine. Nourishes and heals the intestinal lining, preventing the permeability of these tissues by increasing the number of tight junction proteins that link colonocytes to each other, preventing pathogenic organisms from entering the circulatory system. L-glutamine is considered to be a conditionally essential amino acid under normal conditions, because the body can create as much as needed without taking glutamine supplements. But when the digestive system is stressed, for example by ulcers, large amounts of L-glutamine are consumed, and supplements may be necessary to replenish the supply.

L-glutamine is a naturally produced non-essential amino acid that is produced by the breakdown of proteins. L-glutamine is the most abundant amino acid in the bloodstream, and is formed and stored primarily in skeletal muscle and the lungs (and is the primary fuel for enterocytes, essential in their growth, reproduction, and repair). L-glutamine also increases growth hormones, and when ingested has a substantial effect on maintaining and increasing mucosal integrity, including enhancing the integrity of the intestinal mucosa. L-glutamine works by “starting” the formation of nucleotides, which are involved in the production of cellular tissue and the maturation of the intestinal mucosa, and are directly involved in immune processes and energy systems. A diet deficient in glutamine will likely also result in a deficiency in nucleotide formation. Therefore, L-threonine and L-glutamine both act by protecting the inner wall of the stomach by enhancing the integrity of the intestinal mucous membrane.

Although any of the mucogenic amino acids listed above are suitable, the applicant has found that L-threonine works particularly well. L-threonine is a naturally produced essential amino acid and is an important component of the chemical pathway that creates mucin produced by goblet cells distributed throughout the intestinal tract. Other amino acids that contribute to mucin formation include serine, leucine, isoleucine, and cysteine. By aiding metabolism and nutrient absorption, threonine contributes to a smoothly functioning digestive tract. A threonine deficiency slows down the regeneration of the intestinal wall and depresses mucus production. L-threonine is especially useful for wound healing and treating stress, but it is also an essential link in the production of immunoglobulins, boosting immune function.

L-threonine and L-glutamine, which are both naturally produced amino acids produced by the breakdown of proteins, provide additional benefits as well. L-threonine makes up collagen, elastin and enamel protein, aids in metabolism and assimilation, and supports the digestive system by increasing the integrity of the intestinal mucous membrane. The inventors have also observed that L-threonine has a synergistic effect with beta-glucan in further slowing motility through the stomach. L-threonine and L-glutamine are widely available from a number of different suppliers, and they are also powders.

Lecithin acts as an emulsifier that increases the bioavailability of polar and fat-soluble nutrients (including glutamine, threonine, serine and cysteine, as well as many drugs) in the enterocytes lining the intestine. This polar lipid protects and strengthens the intestinal tissue of the digestive system and increases the protective effect of mucus in the digestive tract. This lecithin can be derived from vegetable oil, including safflower, corn, sunflower, oat, or soybean oils. Alternatively, oat oil may be derived from alcohol extraction. Optionally, different vegetable oils such as sunflower oil, safflower oil, olive oil, corn oil or soybean oil can be combined to vary the amount of polar lipids contained in the polar lipid. A form of the dietary supplement that is to be combined in liquid form may contain a mixture of lecithin and sunflower oil (since sunflower oil does not contain a high amount of polar lipids, it can be considered an inactive ingredient). Sunflower or other vegetable oil will generally not be included in the dietary supplement if it is to be combined into a granular or solid form. Among other benefits, polar lipids increase the activity of macrophages, modulating immune function.

The applicant has discovered that the inclusion of lecithin (a polar lipid) plays an important role as it increases the bioavailability of other polar amino acids constituents of the supplement. Polar lipids increase bioavailability through two mechanisms. First, polar lipid digestion products, together with bile salts, can alter the intrinsic transcellular permeability of colonocytes lining the intestine. Second, polar molecules can solubilize with the polar lipid, facilitating movement through the aqueous diffusion layer. The applicant theorizes that this mechanism is related to the ability of the polar lipid to attract polar target molecules via the polar residue and then use the lipophilic residue to transport these molecules across the cell membrane and into the enterocytes and colonocytes that line the intestine. Applicant has found that both lecithin and oat oil are superior for this enhanced membrane transport.

Polar lipids, particularly lecithin, thus provide a versatile delivery vehicle for drugs and nutrients. Studies have shown that polar lipids can increase the bioavailability of co-dissolved lipophilic or polar drugs, including steroids, antibiotics, antihistamines, and anti-nausea drugs. In addition to their use as emulsifiers, polar lipids physically increase the protective effect of mucus in the digestive tract. There are several potential sources of polar lipids that can be used as a polar lipid in the dietary supplement of the present invention. In the preferred embodiment, soybean oil lecithin is used.

Other oils that are also good sources of polar lipids are oat oil, sunflower oil, safflower oil, soybean oil, olive oil, palm oil, corn oil, rapeseed oil, linseed oil, etc. The preferred concentration of polar lipids used in the dietary supplement of the present invention ranges from about 1% to about 15% of the dietary supplement by weight. A typical value is 10%. The term “about” is used throughout this application to allow for manufacturing tolerances of typical formulations readily appreciated by those skilled in the art. Unless otherwise specified herein, all percentages of dietary supplement constituents are percentages of the dietary supplement by weight.

The applicant has discovered that lecithin works particularly well in increasing the absorption bioavailability rate of L-glutamine and the mucogenic (largely polar) amino acid(s). Particularly, the applicant has discovered that, by including lecithin, the bioavailability and absorption rate of L-glutamine and the mucogenic amino acid(s) are considerably greater than what they present in nature. As a result, the dietary supplement, particularly its inclusion of lecithin, results in a compound that has markedly different characteristics than any of its naturally occurring constituents, or any related combination of naturally occurring components.

As mentioned above, embodiments of the present invention also include various prebiotics that are provided to target the specified microbiota and parts of the GI tract. The inclusion of the prebiotic beta-glucan has several advantages. For example, it is a powerful immune system stimulator. Beta-glucan also reduces LDL cholesterol in the bloodstream. It also binds to other sugars and releases them over a period of time, reducing sugar highs and lows thereby stabilizing blood sugar levels. In the preferred embodiment, the beta-glucan used is soluble oat fiber, an oligosaccharide that is found in the oat grain and is a powder when dried. Alternative sources of beta-glucan are barley, yeast and other plant sources. Beta-glucan is a gelling agent that works with gastric juices or water. In one embodiment, the soluble fiber used is beta-glucan which is derived from oats. Other soluble fibers that are also good sources of beta-glucan are those derived from barley or soybeans. Beta-glucan is widely available from a number of different suppliers, and can be ground into a flour.

The prebiotic combination mentioned above also includes FOS. The applicant has also found that the inclusion of FOS also provides a significant advantage. In fact, butyrate is known as an important nutrient for enterocytes and colonocytes. In fact, butyrate is known to be an anticarcinogen and the preferred food for the intestinal lining, helping to heal cells and strengthen the tight junctions between them, limiting permeability. However, butyrate has the smell of rancid butter and is unpleasant. Therefore, it is not desirable to introduce butyrate as a direct constituent of the supplement. The inclusion of FOS promotes the growth of certain commensal bacteria which, in turn, produce butyrate. In other words, the inclusion of FOS allows the generation of butyrate internally and its consequent benefits are achieved. Therefore, another advantage of the invention is the introduction of butyrate without its unpleasant odor.

The prebiotic combination mentioned above also includes RS-4 and arabinoxylan oligosaccharide. RS-4, a resistant chemically modified corn starch, is a prebiotic that works primarily in the transverse and descending colon, supporting beneficial microbes, especially Lachnospiraceae and Roseburia species, in this area of the GI tract. Arabinoxylan oligosaccharide (AXOS) is a prebiotic that works primarily in the descending colon and rectum, supporting beneficial microbes, especially Veilonella and Prevotella species, in this area of the GI tract.

As a result, a spectrum of prebiotics is provided in the dietary supplement, each acting over a defined range of pH and oxygenation to target microbes located in distinct segments of the GI tract, from the distal ileum to the rectum. In fact, FOS primarily functions in the distal ileum and ascending colon. Beta-glucan works mainly in the ascending and transverse colon. RS-4 functions primarily in the transverse and descending colon. AXOS works primarily in the descending colon and rectum. As such, the dietary supplement according to the present invention targets specific microbes found in different areas of the GI tract to provide overlapping coverage, segment by segment. This spectrum is summarized in Figure 2.

Prebiotics are complex sugars that are not digested by human GI tract enzymes. Therefore, these sugars enter the colon intact and represent a source of energy for the colonic microbiota, including in particular certain species of Lactobacillus and Bifidobacterium. These microbes act as key species maintaining a balanced intestinal homeostasis through the formation of short-chain fatty acids. . They lay the groundwork for cross-feeding interactions with other commensals, including beneficial Clostridium, Ruminococcus, and Eubacterium species.

Fermentation of prebiotics lowers the pH in the intestine, inhibiting the degradation of peptides and the subsequent production of toxic compounds including ammonia and amines, and decreases the activity of dysbiotic bacterial enzymes. Some types of commonly combined prebiotics, including inulin, cause excess gas and bloating and are therefore excluded in the present invention.

The applicant has performed necropsies on 111 horses, collecting bacterial swabs from different areas of the colon. The applicant found that as the colonic environment changed from pH 5.5 to pH 7 at the distal end, the types of bacteria that populated those various quadrants of the colon changed. The applicant also found that oxygen was depleted with distance through the intestine, favoring anaerobic microorganisms towards the distal end. The applicant has found a similar distribution of microbes in the human intestine, again with higher pH and less oxygen towards the distal end.

Each type of prebiotic in the present invention targets specific microbes that occupy these unique pH and anaerobic habitats. Each of these niches has different levels of acidity and oxygenation. A single prebiotic is not capable of addressing these highly varied environments, but the arbitrary mix of prebiotics found in many products is not ideal either. Instead, the present invention addresses five specific habitats, each with a different pH and oxygen range, roughly corresponding to the ileum, the ascending, transverse and descending colon, and the rectum. Furthermore, the selected prebiotics mainly affect key species that have the greatest impact on microbial communities. This novel approach allows the treatment of patency problems throughout the colon as well as the distal ileum.

Oligosaccharides (OS) such as XOS, GOS and FOS increase the number of Bifidobacterium (bifidogenic) and Lactobacillus species while decreasing the number of E. coli, enterococci, Clostridium difficile and Clostridium perfringens pathogens. FOS increases the number of butyrate-producing species, including F. prausnitzii, E. rectaleyR. inulinovorans.FOS works best for a bifidogenic effect at pH 6.8, while GOS works best for a bifidogenic effect at pH 6.

Arabinoxylan oligosaccharides (AXOS) derived from oat bran act on Bifidobacterium species in the distal colon and stimulate propionate-producing microbes. Although Bifidobacterium species do not produce butyrate, they do produce acetate and lactate that are metabolized by Anaerostipes, Eubacterium hallii, and other butyrate-producing species.

These oligosaccharides impact the entire colon, but primarily affect the distal ileum and ascending colon, with the exception of AXOS which targets the distal colon and rectum.

Polysaccharides such as beta-glucan increase the number of Bacteroides and Clostridium beijerinckii species, but do not affect the number of Bifidobacterium or Lactobacillus species. Guar gum is another polysaccharide that helps lower pH and increases the number of beneficial Streptococcus thermophilus. These polysaccharides have the greatest effect on microbial populations in the ascending and transverse colon.

Resistant starch (RS) such as RS-4 increases the number of Bifidobacterium and Parabacteroides distasonis while decreasing the number of Firmicutes. RS-4 and its analogs increase the number of butyrate-producing Ruminococcus bromii. The present invention uses a resistant fiber RS-4, which has been chemically cross-linked by a sulfur bond to make it resistant to normal digestive enzymes in the first two segments of the colon, namely, the ascending and transverse sections. In this chemically cross-linked form, RS-4 remains intact in the descending colon and rectum where it can be digested by bacteria in an environment with a pH of 6.8 to 7.0.

Resistant starch has its greatest impact on microbial communities in the transverse and descending colon, as well as some activity in the rectum.

Another direct advantage of the present invention is the ability to allow L-glutamine and other polar mucogenic amino acid(s) to provide their beneficial healing and strengthening of the intestinal lining before increasing the intestinal activity due to the prebiotics mentioned above. As mentioned above, this advantage is achieved mainly by the inclusion of a polar lipid, in this case, lecithin, which advantageously increases the bioavailability of the aforementioned amino acids. Figure 3 illustrates a graph of amino acid absorption rate versus time in minutes. As can be seen in this view, absorption with lecithin present is significantly earlier than without lecithin, and significantly earlier than with fiber alone.

One or more additional constituents may be included. One such preferred additional constituent consists of mannan or mannan oligosaccharides (MOS), which are saccharides that bind to pathogens and cause them to be excreted. Mannan and mannan oligosaccharides are similar to receptors found on the surface of enterocytes and colonocytes that are the target of pathogens. The mannan and mannan oligosaccharides in the dietary supplement bind strongly to pathogens and prevent them from binding to the intestinal lining, thus causing them to be excreted. In the dietary supplement of the present invention, mannan and mannan oligosaccharides are naturally derived from the cell wall of Saccharomyces cerevisiae (brewer's yeast), a yeast extract, although other sources of mannan oligosaccharides are also acceptable.

To prevent the various constituents of the dietary supplement from separating, an emulsifier can also be used. One such emulsifier is guar gum (also known as guaran), a galactomannan oligosaccharide that is extracted from the seed of the leguminous shrub Cyamopsis tetragonoloba. Guar gum is commonly used as an emulsifier, thickener, and stabilizer. It also acts as a prebiotic fiber.

In one embodiment, additional ingredients may be included in the dietary supplement of the present invention to bind and eliminate pathogenic bacteria, to absorb and sequester pathogens, to absorb or soak mycotoxins, and to support the renewal and growth of cells lining the intestine.

Optionally, a nutricin can be used that binds to the pathogens and passes through the digestive system along with the bound pathogen and is excreted in the feces. This additional constituent consists of mannan or mannan oligosaccharides (MOS), which are complex sugars used to bind pathogens while nourishing beneficial bacteria. Mannan or mannan oligosaccharides bind to binding sites on pathogenic bacteria, preventing pathogenic bacteria from binding to receptors on the membrane of enterocytes. Mannan or mannan oligosaccharides are naturally derived from the cell wall of Saccharomyces cerevisiae (brewer's yeast), a yeast extract, although other sources of mannan or mannan oligosaccharides are also acceptable.

Optionally, a pathogenic bacteria absorbent material can be used that attracts bacteria and passes through the digestive system together with the absorbed pathogenic bacteria and is a pathogen absorbent such as the material sold under the trademark SAFMANNAN by S. I. Lesafre, Cedex, France. Other pathogenic bacteria absorbing nutricins that could be used instead include the material sold under the trademark BIOSAF by S. I. Lesafre, the material sold under the trademark BIO-MOS by Alltech, Inc., in Nicholasville, Ky., as well as any another mannan oligosaccharide (complex mannose sugars derived from the yeast cell wall).

Optionally, a mycotoxin absorber also based on Saccharomyces cerevisiae can also be used to absorb or soak mycotoxins in the colon. One such mycotoxin-absorbing nutricin is a material sold under the trademark MYCOSORB by Alltech, Inc. Other mycotoxin-absorbing nutricins that could be used instead include the material sold under the trademark MYCOFIX PLUS by Biomin Distribution, Inc. and the material marketed under the trademark D-MYCOTOC by Kanzy Medipharm, Inc.

An optional active ingredient that may be included in the dietary supplement of the present invention is a nucleotide-containing supplement, which may be incorporated into the rapidly renewing intestinal lining. Dividing cells can use exogenous nucleotides to enhance their replication. The intestinal wall has a series of tiny finger-shaped processes of mucous membrane called villi that serve for the absorption of nutrients, with crypts located between adjacent villi. The crypts house stem cells that proliferate and push enterocytes upward along the villi, continually renewing the tissues. Studies have shown that dietary nucleotides increase the height of the villi, which in turn increases the uptake of nutrients into the body and the effectiveness of other nutritional elements. There are several sources of nucleotides, the best of which are derived from brewer's or baker's yeast.

Finally, there is a non-active ingredient that is added to the dietary supplement of the present invention as an emulsifier to prevent its constituents from separating. The emulsifier used in the dietary supplement in this particular embodiment is guar gum, which also has thickening and stabilizing properties. Other emulsifiers having appropriate properties could be used instead of guar gum, such as carrageenan, xanthan and agar.

Those skilled in the art will immediately appreciate that the dietary supplement of the present invention is much more than simply the sum of its ingredients, the combination of ingredients producing a synergistic and highly effective result. For example, polar lipid acts as a spreading agent that enhances the effectiveness and speed of action of polar amino acids by enhancing their transport across the cell membranes that line the entire digestive tract. Prebiotic fiber slows the passage of polar lipid and amino acids, giving both more time to provide their beneficial effects in the digestive tract. Amino acids also increase the integrity of the intestinal membrane by increasing the number of tight junctions, but they are much more effective and show faster action in combination with the polar lipid than they would be without it.

The relative ranges of amounts of each of the ingredients, and their preferred amounts, are hereby discussed.

Amino acids: Nutricins that increase the integrity of the intestinal mucosa in this embodiment of the present invention include L-glutamine and at least one of the mucogenic amino acids mentioned above.

The range of amounts of the at least one mucogenic amino acid is between about 0% and about 10% each of the dietary supplement by weight. As a non-limiting example using L-threonine, L-threonine is approximately 10% of the dietary supplement by weight.

The range of amounts of L-glutamine is between about 1% and about 20% of the dietary supplement by weight. However, it is believed that less than 2% L-glutamine will result in a reduced effective result. As a non-limiting example, the amount of L-glutamine is approximately 5% of the dietary supplement by weight.

Polar Lipids: The concentration of polar lipids in the present invention can range from about 1% to about 15% of the dietary supplement by weight. Sunflower or other vegetable oil may be added as a diluent to produce a liquid dietary supplement. Polar lipids, usually in the form of lecithin, are derived from oils such as oat oil, sunflower oil, safflower oil, corn oil or soybean oil. These polar lipids can be diluted with other vegetable oils to create liquid or paste formulations of the present invention.

Prebiotics: The range of amounts of prebiotics discussed above, i.e. FOS, beta-glucan, AXOS and RS-4 is between approximately 1% and approximately 40% each of the dietary supplement by weight. The preferred amount of prebiotic fiber is between about 1% and about 40% of the dietary supplement by weight. The most preferred amount of prebiotic fiber is approximately 25% of the dietary supplement by weight. FOS can be derived, for example, from yacon root, chicory root, Jerusalem artichoke, blue agave, acacia, or another fiber-rich vegetable. Beta-glucan can come from, for example, oats, barley, mushrooms, seaweed, algae or yeast cell walls. AXO<s> may be derived, for example, from the bran tissues of wheat, oats, barley, rice, millet, psyllium, flax or rye. RS-4 can be derived from oats, yacon root, chicory root, flax, acacia, corn or bacterial fermentation, and then undergo chemical cross-linking to decrease digestibility by human acids and enzymes.

In those embodiments that include a nutricin that binds to and kills pathogenic bacteria in the digestive tract, such as, for example, pure mannan or mannan oligosaccharide, it may be present at about 0.5% to about 20% of the dietary supplement by weight.

In those embodiments, an emulsifier is also included to prevent the constituents of the dietary supplement from separating, such as, for example, guar gum, which may be present at about 1% to about 5% of the dietary supplement by weight. .

The dietary supplement of the present invention can be manufactured as a solid, as a granulated solid, as a powder, as a paste or as a liquid. In order to manufacture it as a solid, a small amount of oat bran or oat flour (or substitutes thereof) is added to thicken it into the food bar form. It can also be pressed into pill form. It can be added to additional ingredients to make a conventional sized healthy bar. By adding a higher percentage of oat bran or oat flour while stirring the mixture, a granular form of the supplement can be manufactured. This granular form can be sprinkled on cereal or fruit, or added to a liquid. By adding even more flour while stirring the mixture, a powder form of the supplement can be made.

By adding more oil (oat oil, sunflower oil, safflower oil, or another oil), the mixture can be brought to a paste that has the consistency of peanut butter. In paste form, the dietary supplement of the present invention can be stored in gelatin capsules (such as liquid-filled softgel capsules), which also provide a constant dosage of the dietary supplement. By adding even more oil, it can become a viscous liquid that can be swallowed with a spoon.

It is desirable that the dietary supplement of the present invention be taken on a regular basis, which in the preferred embodiment is daily to maintain an optimal level of the ingredients in the digestive tract. The preferred dosage is between about half a teaspoon and about three tablespoons per day. The dietary supplement of the present invention can be taken orally at least once, and possibly two or three times, per day.

The weight of the dietary supplement varies depending on its form, with the paste form having a specific density of approximately 0.8, and the granular or flour forms having a specific density of between 0.5 and 0.6. Therefore, the preferred dosage of the dietary supplement of the present invention can range from about one gram to about thirty grams per day.

Since the dietary supplement of the present invention increases the absorption of nutrients (through the action of polar lipids) in the enterocytes and colonocytes lining the intestine and slows the motility of food through the digestive tract, experts Those in the art will appreciate that when administering a medication orally along with the administration of the dietary supplement, the medication will also spend more time in the digestive tract. This will increase the absorption of the medication and thereby act to enhance the therapeutic effect of the medication. If desired, the medication may be administered at the same time as the dietary supplement is administered, or mixed or suspended in the dietary supplement prior to administration of the dietary supplement.

Upon disclosure of the dietary supplement of the present invention to those skilled in the art, they will immediately appreciate that the dietary supplement is more than simply the sum of its ingredients. The combination of ingredients described produces a synergistic result that is substantially more effective than a sum of the results that would be produced if each ingredient were used by itself. In addition to the utility of the supplement of the present invention in the treatment and prevention of various disorders of the digestive tract, the dietary supplement of the present invention also has utility in the treatment and prevention of various disorders related to the immune system. Depending on the particular desired application of the dietary supplement of the present invention, additional constituents such as vitamins and minerals may also be added thereto.

Examples of vitamins that could be added include vitamins B6, B12, biotin, C, D, E and niacin. Examples of mineral micronutritional additives that may be added include calcium, chromium, copper, magnesium, manganese, phosphorus, potassium, selenium, vanadium and zinc. Other amino acids such as alpha-lipoic acid (ALA) and taurine can also be added. Other supplements could be added, such as, for example, a diabetes supplement, coenzyme Q10 (CoQ10), inositol, and evening primrose oil. Those skilled in the art will appreciate that customized formulations could be prepared for application with specific disorders related to the immune system and the digestive system.

Treatment goals

The present invention, in one or more of its preferred embodiments, aims to prevent, improve or cure diseases related to intestinal dysbiosis and immune problems. Inflammation caused by a dysbiotic microbiota is at the root of dozens of chronic diseases, which are organized here into six categories: intestinal inflammation, systemic inflammation, neurological inflammation, antibiotic-induced inflammation, autoimmunity, and chemotherapy. The teachings herein contemplate not only the supplement itself, but also a method of treatment using the supplement. Such a method includes preparing an appropriately sized dose of the supplement, and administering the supplement. The method may also include first identifying a treatment population based on the conditions, and/or based on concurrent treatment. Additionally, the method may include specifically diagnosing an individual or group with any of the immune system or digestive system related disorders described herein.

intestinal inflammation

Intestinal inflammation is the first and most direct effect of dysbiosis. It takes the form of ulcers, IBS, IBD (including ulcerative colitis and Crohn's disease), diverticulitis, dietary insufficiencies, colon cancer and rectal cancer. Each of these syndromes is associated with leaky gut. The present invention includes prebiotics designed to feed commensal bacteria which, in turn, produce butyrate, a short chain fatty acid. Butyrate is the primary source of metabolic energy for the enterocytes and colonocytes that line the intestine. This helps seal the tight junctions between cells, minimizing permeability and reducing the chances of inflammation. This helps prevent and treat ulcers, IBS and IBD.

Ulcers: The polar lipid lecithin is a component of mucus, and forms a continuous hydrophobic sheet-like layer that protects the mucus and the underlying intestinal wall, providing protection from acids, peptides and pathogens throughout the intestine. Polar lipids, therefore, enhance the impermeability of the enterocytes that line the intestine and protect against ulcers. Glutamine and threonine are known to be limiting reagents in the creation of mucus, the mucus layer decreases in cases of ulcerative colitis (UC), making the intestine susceptible to infections and diseases. Oral administration of lecithin has been shown to enhance the mucus layer. In a placebo-controlled trial, 53% of treated UC patients achieved remission, compared with 10% of patients receiving placebo.

IBS: IBS is a disease of fluctuating intestinal permeability. Prebiotic fiber, polar lipids, and certain amino acids may help increase the impermeability of the intestine, reducing symptoms and leading to remission over time. The caveat with IBS is to avoid treatment during a flare-up of symptoms, as the gut may be too permeable at that time to accommodate any fermentative substrate.

Diverticulitis: This application of the dietary supplement of the present invention is based on the observation that intestinal flow improves due to the presence of polar lipids and prebiotic fiber in the diet. Diverticulitis is caused by the trapping of food particles in pouches or diverticula of the small intestine. Soluble beta-glucan fiber helps slow down transit time, helping the body digest food better. The formula contains polar lipids that help coat the digestive system, improving its impermeability and making it more slippery. This helps prevent particles from getting stuck and building up in the diverticula.

Dietary insufficiencies in the elderly: This application of the dietary supplement of the present invention can help the elderly deal more effectively with a compromised digestive system. This app is based on evidence that glutamine and prebiotic fiber can help increase intestinal muscle tone and boost the immune system. Soluble beta-glucan fiber is known to slow digestive transit, which moderates the bolus, allowing water to be reabsorbed and preventing diarrhea while providing a bulking agent that minimizes constipation. The result is better tone, more predictable elimination and less gastric discomfort.

Colon/rectal cancer: Butyrate regulates the apoptosis and differentiation of colonocytes, eliminating and replacing dysfunctional cells, thus helping to protect against colon cancers. Studies have shown that dietary fiber consumption is inversely correlated with large intestine cancer. Prebiotic fiber reduces relative risk between the lowest and highest quintiles by 60%. In populations with low fiber intake, such as most of the modern world, doubling fiber intake can reduce the risk of colorectal cancer by 40%. In particular, grain fiber, including beta-glucan and FOS, has been shown to decrease the risk of rectal cancer. Similar results were also found in a study with 500 Chinese subjects, expanding on results from Western diets.

Systemic inflammation

Systemic inflammation leads to heart disease, type 2 diabetes, various cancers, allergies and other chronic diseases. By reducing dysbiosis and decreasing systemic inflammation, the present invention prevents, treats and can even cure these diseases of inflamed organs. Additionally, omega-3 polyunsaturated fatty acids (n-3 PUFA) are known to help targets of inflammation, such as the heart and pancreas, but modern diets do not include enough omega-3s in the diet. The polar lipids in the present invention enhance the bioavailability of omega-3 in the diet. They have a synergistic effect on increasing plasma and RBC n-3 levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). The choline head of the polar lipid molecule lecithin attracts and binds hydrophilic substances such as oligosaccharides and therefore increases their bioavailability.

Type 2 diabetes: A dysbiotic microbiota is associated with type 2 diabetes and its associated diseases, including diabetic retinopathy, hypertension, diabetic foot ulcers, and others. By reinforcing the impermeability of the intestinal lining and limiting inflammation through the microbiota, the prebiotic fiber in the present invention can prevent, treat or cause remission of type 2 diabetes. Prebiotic fiber slows digestive transit, which reduces effectively the glycemic index of the food. Soluble beta-glucan fiber is a dietary fiber that absorbs and sequesters starches and sugars, releasing them over a longer time. The result is a low glycemic index, which provides a slow release of sugars into the blood. This reduces the need for insulin to respond to large changes in blood sugar levels, allowing people with a compromised pancreas to deal better with their nutrition. People with only a slight tendency toward diabetes can forego daily insulin injections as long as they continue to use the dietary supplement of the present invention.

Other chronic diseases: Similarly, other diseases that are associated with inflammation can be prevented or treated by prebiotics and amino acids, enhanced by polar lipids, in the present invention. These components of the formula act as food for the gut and food for the microbiota, both of which contribute to a resilient and impermeable intestinal lining, greatly reducing systemic inflammation.

Neurological inflammation

Neurological inflammation can evolve from the gut, via various gut-brain pathways, including the vagus nerve, hormones, and immune system cytokines.

Parkinson's and Alzheimer's: Parkinson's begins with accumulations of proteins called Lewy bodies in infected intestinal cells that make their way to the brain over a period of years. Alzheimer's may also represent the movement of misfolded amyloid proteins from the intestine to the brain. Depression and anxiety are also related to a dysbiotic microbiota. By balancing gut microbes through a blend of prebiotic fibers, Alzheimer's and Parkinson's can be prevented.

Depression and anxiety: Prebiotic fiber has also been shown to reduce depression and anxiety in both animals and humans. The mechanism is based in this case on the fermentation of prebiotic fiber to give butyrate, which can pass the blood-brain barrier to enter the brain. Butyrate alters gene expression in the brain, nourishing and improving the health of neurons. Furthermore, microbes fed selected prebiotics such as those of the present invention can directly produce neurotransmitters including dopamine and serotonin, the targets of many antidepressants and anxiolytics.

Antibiotic-induced inflammation

Antibiotics are commonly used in hospital settings both preoperatively and postoperatively to reduce the chance of infection. However, oral antibiotics carry a significant risk of dysbiosis because broad-spectrum antibiotics will destroy beneficial as well as pathogenic bacteria. Since a balanced set of bacteria is necessary to avoid dominance of any single species, dysbiosis can lead to a toxic overload of spore-generating bacteria that can survive antibiotics. In particular, the sporulating species Clostridium difficile can easily take over the gut microbiota and cause disease and even death by damaging the intestinal lining and allowing systemic inflammation through the translocation of bacteria through the intestinal lining. The amino acids L-glutamine and L-threonine can help heal and protect the intestinal lining, while specifically targeted prebiotics can help nourish a better balanced microbiota, overcoming the complications of antibiotic-induced inflammation.

Some doctors now recommend probiotic supplements, especially multi-species formulations such as yogurt and kefir, as a enhancer and restorer alongside antibiotic treatments to repopulate the gut microbiota. Due to the amino acids in the present invention, the intestinal lining can repair itself in advance of these population growths, helping to ensure that any bacterial blooms can be contained in the intestine. The locally acting prebiotics included in the present invention promote the complex communities of bacterial species required to form a balanced microbiota. Therefore, the present invention can be used as an important adjuvant to oral antibiotic therapies.

Autoimmunity

Autoimmunity can be caused by mimicry, where bacteria or their products imitate existing body tissues. When the immune system attacks these foreign particles, it can also attack normal tissues that share the antigenic properties of the pathogen. Autoimmune diseases include arthritis, lupus, type 1 diabetes, and multiple sclerosis (MS). To the extent that prebiotics reduce pathogen load and thereby silence the immune response, the present invention works to prevent autoimmune diseases.

Arthritis, lupus, type 1 diabetes and MS: These autoimmune diseases are associated with microbiota dysbiosis. Prevotella bacteria are involved in the pathogenesis of rheumatoid arthritis, and prebiotics contribute to bacteria that compete with these pathogenic species. Certain strains of Lactobacillus are depleted in lupus, leading to intestinal permeability, and prebiotics can rebalance the microbiota to decrease symptoms. MS is an inflammatory disease that has a unique microbiota, with higher abundances of Methanobrevibacter and Akkermansia species. Type 1 diabetes is associated with a microbiota that is dominated by Bacteroidetes species and depleted in butyrate-producing bacteria. The prebiotics in the present invention, together with amino acids and enhanced by polar lipids, may help prevent these diseases. To the extent that increasing intestinal integrity improves symptoms in these diseases, the present invention may provide relief. However, once the immune system has targeted one's tissue, it is difficult or impossible to reverse it with the current state of the art.

Chemotherapy

Chemotherapy and radiation treatments work by attacking rapidly dividing cells, including those in the intestinal lining. Such cancer treatments can lead to leaky gut, inflammation, and therefore all of the diseases listed above. Specific diseases directly attributable to cancer treatments include mucositis, stomatitis, and cachexia. In addition to these side effects of traditional cancer therapy, there are new therapies that depend on the microbiota to be effective. Because all of these diseases are related to the intestine, they can be improved by the polar lipids, prebiotic fiber and amino acids of the present invention.

Mucositis and stomatitis: Chemotherapy depletes glutamine, and this formula helps compensate for that imbalance. Glutamine taken orally can significantly reduce the duration and severity of mucositis during and after radiation therapy. It has also been shown that glutamine can reduce the effects of mucositis during bone marrow transplantation. The dietary supplement embodiment of the present invention for this application may include a higher percentage of glutamine, up to twenty percent (five grams per dose). In addition to glutamine, the formula includes threonine, which is essential for mucus production. Polar lipids such as lecithin are known to increase the bioavailability of amino acids in the formula many-fold, thereby reducing the total amount of amino acids required. This is an important aspect of the dietary supplement of the present invention, since the patient may have difficulty eating or drinking. Additionally, this application of the dietary supplement of the present invention incorporates small doses of zinc and vitamin B-12, which are also known to help relieve symptoms of mucositis and stomatitis. Therefore, the dietary supplement of the present invention may help people recover faster from cancer therapies, and possibly increase the recovery rate.

Cachexia: This application of the dietary supplement of the present invention can help a person with wasting disease, or cachexia, gain weight and therefore accelerate their recovery. It has been established that glutamine is useful for HIV and cancer patients who are cachexic. Glutamine is an abundant amino acid, but in times of stress, the digestive system may not get enough to properly maintain its high growth rate. The dietary supplement of the present invention contains glutamine together with polar lipids to improve the bioavailability of this polar amino acid. It also includes threonine, which is an integral part of the mucus-generating pathway. Mucus, in turn, helps maintain the barrier between the body and the digestive system. Improving this barrier can help prevent blood or serum loss that can contribute to wasting.

Checkpoint inhibitors: New cancer treatments involving immune checkpoint inhibitors depend on a well-balanced microbiota. These new therapies involve harvesting T cells, modifying them to attack cancer cells, and then reinjecting them into the patient to treat cancers such as advanced melanoma, renal cell carcinoma, and non-small cell lung cancer. Certain bacteria, especially Clostridium species and Akkermansia muciniphila, reduce the effectiveness of immune checkpoint inhibitors. By supplying the intestine with appropriate fiber, beneficial species can modulate the number of these harmful bacteria and improve the effectiveness of these particular anti-cancer drugs. In this way, the prebiotic fibers in the present invention can augment these immune cell therapies.

Therefore, it can be seen from the above detailed description of the preferred embodiment of the present invention that it teaches a dietary supplement that effectively treats disorders of the digestive tract, decreasing permeability by nourishing both the cells that line the intestine and the beneficial bacteria. of the microbiota. As a consequence, systemic inflammation is reduced or eliminated, leading to the prevention, treatment or possible cure of many chronic diseases in humans and potentially other animals as well.

The dietary supplement of the present invention consists entirely of safe and natural ingredients instead of drugs. The dietary supplement of the present invention can be administered orally, thus making its dispensing a simple matter. The dietary supplement of the present invention can be combined into a paste, solid, liquid, powder or a form that can be added to liquids for administration. The dietary supplement of the present invention may also be packaged in a manner that facilitates shipping and storage.

The dietary supplement of the present invention is stable and has a long shelf life, and does not require any special care from the user throughout its shelf life before use. The dietary supplement of the present invention is also economical relative to previously known treatments of digestive tract disorders and treatments of immune-related disorders, thereby enhancing its market appeal and providing it with the widest possible market. Finally, all of the above-mentioned advantages and objectives of the dietary supplement of the present invention and its method of administration are achieved without incurring any substantial relative disadvantages.

Although the foregoing description of the present invention has been shown and described with reference to particular embodiments and applications thereof, it has been presented for illustrative and descriptive purposes and is not intended to be exhaustive or to limit the invention to the particular embodiments and applications disclosed.

The particular embodiments and applications have been chosen and described to provide the best illustration of the principles of the invention and its practical application to thereby enable one skilled in the art to use the invention in various embodiments and with various modifications that are suitable for the private use contemplated. All such changes, modifications, variations and therefore alterations shall be deemed to be within the scope of the present invention as determined by the appended claims when construed to the extent to which they are fairly, legally and equitably entitled.

The use of the terms “a” and “an” and “the” and similar referents in the context of the description of the invention (especially in the context of the following claims) should be interpreted as covering both the singular and the plural. , unless otherwise indicated herein or clearly contradicted by the context. The terms “comprising,” “having,” “including,” and “containing” should be construed as open terms (i.e., meaning “including, but not limited to,”) unless otherwise indicated. contrary. Reference to ranges of values herein is intended solely as shorthand for referring individually to each separate value within the range, unless otherwise indicated herein, and each separate value is incorporated in the specification as if it were mentioned individually herein. All methods described herein may be performed in any suitable order unless otherwise indicated herein or clearly contradicted by the context. The use of any and all examples, or exemplary expressions (e.g., “such as”) provided herein, is intended simply to better illuminate the invention and does not pose a limitation on the scope of the invention to unless otherwise claimed. No expression in the specification should be construed as indicating that any unclaimed element is essential to the practice of the invention.

Preferred embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. Variations of those preferred embodiments may become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventors expect that those skilled in the art will employ such variations as appropriate, and the inventors intend that the invention be practiced in a manner other than that specifically described herein.

Claims (16)

Yo. A dietary supplement for the treatment and prevention of disorders related to the immune system and the digestive system, said digestive and immune supplement comprising: L-glutamine to support the lining of a GI tract; at least one of the following mucogenic amino acids: L-threonine, L-serine, L-proline, L-cysteine to increase the number and productivity of goblet cells lining the GI tract; lecithin to increase the bioavailability and absorption rate of L-glutamine and at least one mucogenic amino acid; fructo-oligosaccharide that provides at least one beneficial effect on health; beta-glucan that provides at least one beneficial effect on health; RS-4 starch providing at least one beneficial health effect; and arabinoxylan oligosaccharide that provides at least one beneficial health effect. 2. The dietary supplement as defined in claim 1, wherein said L-glutamine is produced by vegan bacterial fermentation of sugar beet, isolated, purified and micronized for faster absorption; and wherein said L-glutamine comprises between about one percent and twenty percent of said dietary supplement by weight. 3. A dietary supplement as defined in any preceding claim, wherein said at least one mucogenic amino acid is produced by vegan bacterial fermentation, isolated and purified. 4. The dietary supplement as defined in any preceding claim, wherein said lecithin is derived from soybean oil, oat oil, sunflower oil, safflower oil or corn oil; and said lecithin comprises between about five percent and about fifteen percent of said dietary supplement by weight. 5. The dietary supplement as defined in any preceding claim, wherein said fructooligosaccharides are derived from yacon root, chicory root, Jerusalem artichoke, or blue agave; and wherein said fructo-oligosaccharides comprise between about one percent and about forty percent of said dietary supplement by weight. 6. The dietary supplement as defined in any preceding claim, wherein said beta-glucan is derived from oats, barley, mushrooms, seaweed, algae or yeast cell walls; and wherein said beta-glucan comprises between about one percent and about forty percent of said dietary supplement by weight. 7. The dietary supplement as defined in any preceding claim, wherein said arabinoxylan oligosaccharide is derived from the bran tissues of wheat, oats, barley, rice, millet, psyllium, flax or rye; and wherein said arabinoxylan oligosaccharide comprises between about one percent and about forty percent of said dietary supplement by weight. 8. The dietary supplement as defined in any preceding claim, wherein said RS-4 starch is derived from oats, yacon root, chicory root, flax, acacia, corn or bacterial fermentation and then undergoes chemical cross-linking to decrease digestibility by human acids and enzymes; and wherein said RS-4 starch comprises between about one percent and forty percent of said dietary supplement by weight. 9. The dietary supplement as defined in any preceding claim, further comprising a nutricin that binds to and eliminates pathogenic bacteria in the digestive tract, the nutricin including at least one pure mannan or mannan oligosaccharide (MOS); and wherein said nutricin that binds to and eliminates pathogenic bacteria in the digestive tract comprises between about one-half percent and about forty percent of said dietary supplement by weight. 10. The dietary supplement as defined in any preceding claim, further comprising guar gum in an amount of about one to five percent of said dietary supplement by weight. 11. The dietary supplement as defined in any preceding claim, wherein said dietary supplement is combined as at least one of a solid food bar or pressed into a pill form, as a paste, as a granulated solid, as a powder , as a liquid or as liquid-filled soft gel capsules. 12. The dietary supplement as defined in any preceding claim, wherein said digestive system disorders are selected from a group comprising ulcers, colitis, irritable bowel syndrome, diverticulosis, diverticulitis, antibiotic-induced inflammation, Crohn's disease, mucositis and stomatitis; or wherein said disorders related to the digestive system are selected from a group comprising cachexia, lactose intolerance and dietary insufficiencies in the elderly. 13. The dietary supplement as defined in any preceding claim, wherein said immune system related disorders are selected from a group comprising arthritis, diabetes, depression, anxiety and heart disease; or wherein said immune system related disorders are selected from a group comprising Alzheimer's, Parkinson's, multiple sclerosis and other neurodegenerative diseases. 14. The dietary supplement as defined in any preceding claim, further comprising at least one vitamin from the group consisting of vitamin B6, vitamin B12, biotin, vitamin C, vitamin D, vitamin E and niacin. 15. The dietary supplement as defined in any preceding claim, further comprising at least one mineral micronutritional additive from the group consisting of calcium, chromium, copper, manganese, magnesium, phosphorus, potassium, selenium, vanadium and zinc. 16. The dietary supplement as defined in any one of the preceding claims for use in the treatment and prevention of dysbiosis and diseases associated with dysbiosis.